scholarly journals Congenital platelet defects.

10.33540/255 ◽  
2020 ◽  
Author(s):  
◽  
Maaike Willemijn Blaauwgeers Blaauwgeers
Keyword(s):  

Author(s):  
J C Walmsley ◽  
A R Lang

Interest in the defects and impurities in natural diamond, which are found in even the most perfect stone, is driven by the fact that diamond growth occurs at a depth of over 120Km. They display characteristics associated with their origin and their journey through the mantle to the surface of the Earth. An optical classification scheme for diamond exists based largely on the presence and segregation of nitrogen. For example type Ia, which includes 98% of all natural diamonds, contain nitrogen aggregated into small non-paramagnetic clusters and usually contain sub-micrometre platelet defects on {100} planes. Numerous transmission electron microscope (TEM) studies of these platelets and associated features have been made e.g. . Some diamonds, however, contain imperfections and impurities that place them outside this main classification scheme. Two such types are described.First, coated-diamonds which possess gem quality cores enclosed by a rind that is rich in submicrometre sized mineral inclusions. The transition from core to coat is quite sharp indicating a sudden change in growth conditions, Figure 1. As part of a TEM study of the inclusions apatite has been identified as a major constituent of the impurity present in many inclusion cavities, Figure 2.



1998 ◽  
Vol 80 (09) ◽  
pp. 437-442 ◽  
Author(s):  
I. Hioki ◽  
K. Onoda ◽  
T. Shimono ◽  
H. Shimpo ◽  
K. Tanaka ◽  
...  

SummaryAlterations in platelet aggregability may play a role in the pathogenesis of qualitative platelet defects associated with cardiopulmonary bypass (CPB). We circulated fresh heparinized whole blood through tubing sets coated with heparin (C group, n = 10) and through non-coated sets (N group, n = 10) as a simulated CPB circuit. Shear stress (108 dyne/cm2)-induced platelet aggregation (hSIPA), plasma von Willebrand factor (vWF) activity and platelet glycoprotein (GP) Ib expression were measured, before, during, and after this in vitro set up of circulation. In the two groups, the extent of hSIPA significantly decreased during circulation and was partially restored after circulation. Decreases in the extent of hSIPA were significantly less with use of heparin-coated circuits. There was an equivalent reduction in plasma vWF activity, in the two groups. Expression of platelet surface GP Ib decreased significantly during circulation and recovered after circulation. Reduction of surface GP Ib expression during circulation was significantly less in the C group than that in the N group. Decrease in surface GP Ib expression correlated (r = 0.88 in either group) with the magnitude of hSIPA, in the two groups. The progressive removal of surface GP Ib was mainly attributed to redistribution of GP Ib from the membrane skeleton into the cytoskeleton. Our observations suggest that use of heparin-coated circuits partly blocks the reduction of hSIPA, as a result of a lesser degree of redistribution of GP Ib.



2001 ◽  
Vol 21 (03) ◽  
pp. 82-96 ◽  
Author(s):  
D. Hoppensteadt ◽  
O. Iqbal ◽  
R. L. Bick ◽  
J. Fareed

SummaryThrombotic disorders are the most common cause of death in the United States. About two million individuals die each year from an arterial or venous thrombosis or related disorders. About 80% to 90% of all cases of thrombosis can now be defined with respect to cause. Of these, over 50% occur in patients who harbor a congenital or acquired blood coagulation protein or platelet defect which caused the thrombotic event. It is obviously of major importance to define those individuals harboring such a defect as this allows: 1) appropriate antithrombotic therapy to decrease risks of recurrence; 2) determination of the length of time the patient must remain on therapy for secondary prevention; and 3) allow for testing of family members of those harboring a blood coagulation protein or platelet defect which is hereditary (about 50% of all coagulation and platelet defects mentioned above). Aside from mortality, significant additional morbidity occurs from both arterial or venous thrombotic events, including, but not limited to paralysis (non-fatal thrombotic stroke), cardiac disability (repeated coronary events), loss of vision (retinal vascular thrombosis), fetal waste syndrome (placental vascular thrombosis), stasis ulcers and other manifestations of post-phlebitic syndrome, etc.



2021 ◽  
Vol 10 (5) ◽  
pp. 894
Author(s):  
Alessandro Aliotta ◽  
Debora Bertaggia Calderara ◽  
Maxime G. Zermatten ◽  
Matteo Marchetti ◽  
Lorenzo Alberio

Platelets are active key players in haemostasis. Qualitative platelet dysfunctions result in thrombocytopathies variously characterized by defects of their adhesive and procoagulant activation endpoints. In this review, we summarize the traditional platelet defects in adhesion, secretion, and aggregation. In addition, we review the current knowledge about procoagulant platelets, focusing on their role in bleeding or thrombotic pathologies and their pharmaceutical modulation. Procoagulant activity is an important feature of platelet activation, which should be specifically evaluated during the investigation of a suspected thrombocytopathy.





1995 ◽  
Vol 1 (4) ◽  
pp. 286-292 ◽  
Author(s):  
Rodger L. Bick ◽  
H. Robert Laughlin ◽  
Brian M. Cohen ◽  
A. Jay Staub ◽  
James Madden ◽  
...  

Fetal wastage syndrome is characterized by recurrent spontaneous abortion. Many syndromes are associated with recurrent fetal loss, including anatomical anomalies, endocrine/hormonal abnormalities, and coagulation defects, with coagulation defects accounting for ∼30% of cases. Most procoagulant factor defects are due to inadequate fibrin-mediated implantation of the fertilized ovum into the decidua. However, blood protein/ platelet defects leading to hypercoagulability and thrombosis are associated with thrombosis of placental vessels, precluding viability of the implanted ovum or later fetus. During the past 2 years, we have seen 46 patients with fetal wastage syndrome due to thrombosis-associated hemostasis defects. In this group, there have been three patients with sticky platelet syndrome, one patient with dysfibrinogenemia, four patients with congenital protein S deficiency, 35 patients with anticardiolipin antibodies, and one patient with a lupus anticoagulant. Patients were started on one low-dose aspirin (ASA), 81 mg per day preconception, at time of diagnosis, and low-dose s.c. porcine heparin at 5,000 units every 12 h was added immediately postconception. The combination of low-dose ASA plus low-dose s.c. porcine heparin was used throughout pregnancy. All patients achieving pregnancy have had uneventful, normal deliveries. It appears that blood protein/platelet defects leading to thrombosis and associated with recurrent fetal loss can be successfully managed with the use of preconception low-dose ASA, followed by immediate postconception addition of fixed low-dose porcine heparin, both used throughout pregnancy. Using this regimen, our success rate has been 100%. Ideal heparin doses, which might be much lower than our empirically chosen and currently used doses, remain to be defined in this particular indication. Key Words: Fetal wastage syndrome—Heparin—Aspirin.



Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2096-2096
Author(s):  
Eric Mou ◽  
Colin Murphy ◽  
Jason Hom ◽  
Lisa Shieh ◽  
Neil Shah

Introduction Platelets are transfused prophylactically to prevent hemorrhage in a variety of patient populations. However, guidelines indicate that prophylactic platelet transfusions in patients with platelet counts above 50k/uL are usually not indicated, with notable exceptions including those undergoing neurological or cardiac bypass surgery. Common minor procedures such as paracentesis, central line placement, and lumbar puncture have been safely performed at platelet counts below 50k/uL. Despite this evidence, our institution incurred approximately 10 million dollars (USD) in direct platelet costs in 2017, with nearly 40% of platelet transfusions are occurring when the patient's platelet count exceeded 50k/uL. Given the significant financial impact of, and potential adverse effects associated with inappropriate platelet transfusion, we implemented a best practice advisory (BPA) in our electronic medical record (EMR) in order to better characterize patterns of platelet transfusion orders in patients with platelet counts >50k/uL. Methods An EMR-embedded BPA was activated in the inpatient hospital setting of a large, tertiary care academic medical center on May 1, 2019, and triggered whenever a platelet transfusion order was placed on an admitted patient whose most recent documented platelet count was >50k/ul. To inform the comparative impact of BPA alerts on provider behavior, alerts were randomized at the patient level to trigger either in standard or silent fashion. For standard alerts, the BPA appeared on-screen, informing the provider that their platelet transfusion order was potentially inappropriate and citing supportive evidence. Providers had the option of following or overriding the alert (Figure 1). In case of alert override, a pre-specified or free text justification was requested. Pre-specified options included upcoming neurosurgery, cardiac bypass surgery, known qualitative platelet defects, or patients taking antiplatelet drugs. Charge data were based on charges for platelet transfusion orders as listed in the hospital charge master. Results From May 1, 2019 to July 30, 2019, the alert fired 181 times (Figure 2). Alerts were silently triggered in 64 (35%) cases. Of the 117 active alerts, 23 (20%) were followed and 94 (80%) were overridden. The most common reasons for alert override included prophylactic transfusions ahead of non-cardiac and non-neurosurgical operations (18%), upcoming cardiac bypass surgery (18%), qualitative platelet defects (12%), active central nervous system (CNS) bleeding (12%), and active non-CNS bleeding (7%). The estimated cost savings associated with followed alerts was $18,170 USD. Discussion Our BPA was effective in reducing instances of platelet transfusion orders by 20% over a three-month period, translating to an estimated annual savings of nearly $70,000 USD in hospital charges. Conversely, the 80% alert override rate indicates that platelet transfusion in patients with platelet counts >50k/uL remains common, occurring in a variety of contexts. Potentially appropriate reasons for platelet transfusions included orders in the setting of cardiovascular bypass surgery, active CNS bleeding, or qualitative platelet defects, representing circumstances in which platelet thresholds are often set higher than 50k/uL. Alternatively, 25% of alert overrides occurred in potentially inappropriate contexts, including patients undergoing non-cardiovascular/non-neurosurgical procedures and patients with non-CNS active bleeding, settings where routinely targeting a platelet threshold >50k/uL is not supported by evidence. As a result of our study's randomized design, future directions include comparative analyses between patient care encounters in which alerts were silently versus visibly triggered, allowing for rigorous determination as to whether providers' interaction with our BPA influences subsequent rates of potentially inappropriate platelet utilization as compared to a control group. Overall, our findings show that platelets are frequently ordered in potentially inappropriate settings, and that reducing these orders imparts significant financial savings. These results provide an impetus for interventions directed at educating providers on appropriate platelet ordering practices, in order to further reduce unnecessary expenditures and optimize patient care. Disclosures No relevant conflicts of interest to declare.



2018 ◽  
Vol 07 (04) ◽  
pp. 185-190
Author(s):  
Emrah Celtikci ◽  
Onur Ozgural ◽  
Umit Eroglu ◽  
Yusuf Caglar ◽  
Fatih Yakar

AbstractOsteogenesis imperfecta, also named as brittle bone disease, is characterized by fragile bones and short stature caused by mutations in the collagen gene. Subdural and intraparenchymal hematomas are defined and associated with trauma, vascular causes, and systemic bleeding diathesis. Skull fragility may lead to epidural hematoma, which is a life-threatening situation. Vascular fragility and intrinsic platelet defects are the causes of bleeding in patients with osteogenesis imperfecta, which is a major management challenge for neurosurgeons. Here, we reported on a 5-year-old boy with osteogenesis imperfecta with epidural hematoma and skull fracture following a trivial trauma, and made a literature review of 28 cases with extra-/intradural hematoma.



Blood ◽  
2020 ◽  
Vol 136 (17) ◽  
pp. 1956-1967 ◽  
Author(s):  
Matthew C. Sims ◽  
Louisa Mayer ◽  
Janine H. Collins ◽  
Tadbir K. Bariana ◽  
Karyn Megy ◽  
...  

Abstract Gray platelet syndrome (GPS) is a rare recessive disorder caused by biallelic variants in NBEAL2 and characterized by bleeding symptoms, the absence of platelet α-granules, splenomegaly, and bone marrow (BM) fibrosis. Due to the rarity of GPS, it has been difficult to fully understand the pathogenic processes that lead to these clinical sequelae. To discern the spectrum of pathologic features, we performed a detailed clinical genotypic and phenotypic study of 47 patients with GPS and identified 32 new etiologic variants in NBEAL2. The GPS patient cohort exhibited known phenotypes, including macrothrombocytopenia, BM fibrosis, megakaryocyte emperipolesis of neutrophils, splenomegaly, and elevated serum vitamin B12 levels. Novel clinical phenotypes were also observed, including reduced leukocyte counts and increased presence of autoimmune disease and positive autoantibodies. There were widespread differences in the transcriptome and proteome of GPS platelets, neutrophils, monocytes, and CD4 lymphocytes. Proteins less abundant in these cells were enriched for constituents of granules, supporting a role for Nbeal2 in the function of these organelles across a wide range of blood cells. Proteomic analysis of GPS plasma showed increased levels of proteins associated with inflammation and immune response. One-quarter of plasma proteins increased in GPS are known to be synthesized outside of hematopoietic cells, predominantly in the liver. In summary, our data show that, in addition to the well-described platelet defects in GPS, there are immune defects. The abnormal immune cells may be the drivers of systemic abnormalities such as autoimmune disease.



Blood ◽  
1974 ◽  
Vol 44 (6) ◽  
pp. 789-800 ◽  
Author(s):  
F. I. Pareti ◽  
H. J. Day ◽  
D. C. B. Mills

Abstract Ten patients with qualitative platelet defects have been investigated. All of the patients had impairment of secondary platelet aggregation induced by ADP, epinephrine, and collagen, and a defective release reaction. In seven patients from four families, the abnormality was consistent with the lack of a metabolically inert adenine nucleotide pool. Four of these patients, from two families, were albinos. Platelets from all of these patients had lower than normal amounts of adenine nucleotides and 5HT; the ability of these platelets to incorporate the amine was reduced and 5HT was metabolized at an abnormally rapid rate in platelet-rich plasma. It was not possible to distinguish the defect present in the albinos from that in the normally pigmented patients. Three other patients had normal amounts of platelet adenine nucleotides and 5HT; platelet aggregation and the release of adenine nucleotides induced by collagen were impaired. Metabolic ATP breakdown, during collagen aggregation, was also decreased. This defect is similar to that induced in normal platelets by aspirin. Studies on intracellular synthesis of cyclic 3'5' AMP in both groups of patients showed that the platelets were normally responsive to PGE1 and the antagonism of PGE1 by ADP and by epinephrine was also normal.



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